In Vitro and in Vivo Antiestrogenic Effects of Polycyclic Musks in Zebrafish
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- 作者：Richard H. M. M. Schreurs ; Juliette Legler ; Elsa Artola-Garicano ; Theo L. Sinnige ; Peter H. Lanser ; Willem Seinen ; and Bart van der Burg
- 刊名：Environmental Science & Technology
- 出版年：2004
- 出版时间：February 15, 2004
- 年：2004
- 卷：38
- 期：4
- 页码：997 - 1002
- 全文大小：107K
- 年卷期：v.38,no.4(February 15, 2004)
- ISSN：1520-5851
文摘
The polycyclic musks 6-acetyl-1,1,2,4,4,7-hexamethyltetraline(AHTN) and 1,2,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-
DER=0 >-2-benzopyran (HHCB) are used as fragranceingredients in perfumes, soaps, and household cleaningproducts. They are known to be ubiquitously present in theaquatic environment, and because of their lipophilicnature, they tend to bioaccumulate in aquatic biota. Insurface waters, concentrations between 1 ng/L and 5 
g/Lhave been found, depending mainly on the proportion ofsewage effluents in the water. In fish, under normalenvironmental conditions, concentrations in the microgramper kilogram fresh weight (fw) range are found. In aprevious study we showed that AHTN and HHCB exertmainly antiestrogenic effects on the human estrogen receptor
(ER) and ER
in an in vitro reporter gene assay. Inthe current study, we assessed the in vitro antiestrogeniceffects of both musks on zebrafish ERs. Antagonismwas observed on zfER, and more pronounced on thenewly cloned zfER. Using a transgenic zebrafish assay,we studied antiestrogenicity of the musks in vivo. Dose-dependent antagonistic effects were observed atconcentrations of 0.1 and 1 M AHTN and HHCB. GC-MS analysis showed that the musks bioaccumulated in thefish, with internal concentrations (15-150 mg/kg fw)which were roughly 600 times higher than the nominaltest doses. To our knowledge, this is the first time thatenvironmental contaminants are shown to be antiestrogenicin an in vivo fish assay that focuses solely on ER-mediated effects. This makes the transgenic zebrafishassay a promising tool for the rapid detection of bothestrogenic and antiestrogenic effects of chemicals in fish.
DER=0 >-2-benzopyran (HHCB) are used as fragranceingredients in perfumes, soaps, and household cleaningproducts. They are known to be ubiquitously present in theaquatic environment, and because of their lipophilicnature, they tend to bioaccumulate in aquatic biota. Insurface waters, concentrations between 1 ng/L and 5 g/Lhave been found, depending mainly on the proportion ofsewage effluents in the water. In fish, under normalenvironmental conditions, concentrations in the microgramper kilogram fresh weight (fw) range are found. In aprevious study we showed that AHTN and HHCB exertmainly antiestrogenic effects on the human estrogen receptor (ER) and ER in an in vitro reporter gene assay. Inthe current study, we assessed the in vitro antiestrogeniceffects of both musks on zebrafish ERs. Antagonismwas observed on zfER, and more pronounced on thenewly cloned zfER. Using a transgenic zebrafish assay,we studied antiestrogenicity of the musks in vivo. Dose-dependent antagonistic effects were observed atconcentrations of 0.1 and 1 M AHTN and HHCB. GC-MS analysis showed that the musks bioaccumulated in thefish, with internal concentrations (15-150 mg/kg fw)which were roughly 600 times higher than the nominaltest doses. To our knowledge, this is the first time thatenvironmental contaminants are shown to be antiestrogenicin an in vivo fish assay that focuses solely on ER-mediated effects. This makes the transgenic zebrafishassay a promising tool for the rapid detection of bothestrogenic and antiestrogenic effects of chemicals in fish.